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Biomedical subjects

D P Evans

Publications and source records attributed to D P Evans.

8 recordsLinked to original sources

Lumbar spinal manipulation on trial. Part I--clinical assessment.

Thirty-two patients with chronic low back pain were treated three times at weekly intervals with rotational manipulation. Patients with femoral or sciatic root pain were included provided they did not exhibit root compression signs. Background therapy of codeine phosphate was administered throughout. There was a significant increase in spinal flexion measured clinically during the three-week period of manipulation followed by a significant decrease in the three-week period after manipulation. The first week of manipulative treatment was more painful than the corresponding week in the control group but in the second and third weeks there was less pain in the manipulated group. Pain scores were reduced to a significant degree within four weeks of starting treatment only in the group manipulated in the first treatment period. Patients benefitting subjectively from manipulation were more likely to be older and to have had symptoms for a shorter period than those not deriving benefit. The age of onset of symptoms was significantly later in the responders.

Adult

Lumbar spinal manipulation on trial. Part II--radiological assessment.

In a trial of manipulation for chronic low back pain, radiographs of the lumbar spine and radiographic assessment of spinal motion were of no value in predicting or assessing the response of the patients to manipulation. Although radiography of the lumbar spine is a commonly requested investigation, it contributes little to the management of such patients except to exclude serious spinal pathology before any form of physical treatment is commenced.

Adult

Studies on the role of histamine and 5-hydroxytryptamine in immunity against the nematode Trichostrongylus colubriformis. IV. Inhibition of the expulsion of worms transplanted into the duodenum of immune guinea pigs.

Significant numbers of fourth larval stage Trichostrongylus colubriformis from sheep donors are expelled from the small intestine of T. colubriformis-immune guinea pigs within 8 h of transplantation into this organ. This model system for the immune expulsion of gastrointestinal nematode parasites was used in the current experiments to examine the effect of drugs recently shown to modify the release of histamine. The experiments showed that worm expulsion was inhibited by the beta-adrenergic agonists salbutamol and isoprenaline, the phosphodiesterase inhibitors aminophylline and ICI 63,197, the antiallergic drug ICI 74,917 and the antihistamine mepyramine. The beta-blocker propranolol prevented inhibition of worm expulsion following salbutamol treatment and there was some evidence of synergistic action between salbutamol and ICI 63,197. The results support previous findings suggesting an important role for histamine release in the effector mechanism of the immune response of guinea pigs against the parasitic nematode T.colubriformis.

Albuterol

Human eosinophils, acidic tetrapeptides (ECF-A) and histamine. Interactions in vitro and in vivo.

The ECF-A acidic tetrapeptides Val-Gly-Ser-Glu, Ala-Gly-Ser-Glu and the analogue Val-Gly-Asp-Glu were selectively chemotactic for human eosinophils over a narrow dose range although eosinophils from different individuals varied in their dose-response pattern. Histamine abrogated the chemotactic properties of the individual tetrapeptides. When Val-Gly-Ser-Glu and Ala-Gly-Ser-Glu were combined in various concentrations the resultant chemotaxis was either negligible or no greater than that produced when each peptide was tested separately. Val-Gly-Ser-Glu and Ala-Gly-Ser-Glu both promoted eosinophil accumulation when applied to the abraded skin of man or i.d. to the marmoset. Biopsies of marmoset skin revealed that peptide-induced eosinophilia was not associated with mast-cell degranulation. Histamine, which was chemotactic in vitro, did not lead to appreciable eosinophil accumulation in vivo, and combinations of histamine and the acidic tetrapeptides evoked little or no cutaneous eosinophil infiltration either in man or the marmoset. These studies suggest that there is a complex interaction between histamine and the ECF-A tetrapeptides; however, the tetrapeptides alone can promote the recruitment and localization of eosinophils by a mechanism apparently independent of mast-cell degranulation.

Animals

The mechansim of tachyphylaxis to ICI 74,917 and disodium cromoglycate.

Pre-incubation in vitro of sensitised peritoneal mast cells for 10 min with either ICI 74,917 (10-5 M) abolished the ability of either drug to inhibit histamine release when subsequently presented to the cells at the same time as antigen. In the case of disodium cromoglycate, tachyphylaxis was abolished by washing the cells after pre-incubation with the drug. The failure to abolish tachyphylaxis to ICI 74,917 was due to the high pre-incubation concentration employed, as at lower concentrations (10-8 M) tachyphylaxis to ICI 74917 was readily abolished by washing. Tachyphylaxis to these anti-allergic agents may be related to a physical blocking of drug receptor sites on or in mast cells.

Animals

Inhibition of immediate hypersensitivity reactions in laboratory animals by a phenanthroline salt (ICI 74,917).

1. The activity of a new anti-allergic compound, I.C.I. 74,917, has been studied in the rat, mouse and guinea-pig. 2. Following intravenous administration, I.C.I. 74,917 inhibits in a dose-dependent manner passive cutaneous anaphylaxis induced in rats and mice by heat-labile homocytotropic antibody. In rats, its potency is approximately 300 times that of disodium cromoglycate. 3. To achieve maximal inhibition, it is necessary to administer I.C.I. 74,917 at the same time as antigenic challenge; dosing before or after challenge has much less effect. 4. Liberation of histamine, provoked by the antigenic challenge of mast cells passively sensitized in vitro by IgE-like antibody, is reduced in the presence of I.C.I. 74,917. 5. Intravenous administration of the compound has no significant effect upon local blueing reactions provoked in the rat by intradermal injection of histamine, 5-hydroxytryptamine or Compound 48/80. It has only a slight effect at high doses upon passive cutaneous anaphylaxis induced in the rat by heat-stable homocytotropic or heterologous (guinea-pig) antibodies. 6. Although not a bronchodilator in the guinea-pig, I.C.I. 74,917 partially inhibits systemic anaphylaxis. A consistent reduction in the severity of antigen-induced bronchospasm was demonstrated in the Konzett-Rossler preparation at doses comparable to those inhibiting passive cutaneous anaphylaxis in the rat. However, there was only slight inhibition of passive cutaneous anaphylaxis in the guinea-pig. 7. I.C.I. 74,917 itself induces bronchospasm when administered to anaesthetized guinea-pigs or to a guinea-pig isolated lung preparation. This effect is reversed by salbutamol, but is not prevented by the prior administration of mepyramine, atropine or methysergide. 8. These results indicate that in the rat, mouse and guinea-pig, I.C.I. 74,917 is a potent inhibitor of certain types of immediate hypersensitivity reactions.

Anaphylaxis

Inhibition of immediate hypersensitivity reactions in the rat by ICI 74,917 and disodium cromoglycate.

ICI 74,917, a potent inhibitor of IgE-mediated passive cutaneous anaphylaxis (PCA) in the rat, exhibited tachyphylaxis in that pre-dosing sensitised rats with a high dose of compound reduced the inhibitory effect on rat PCA of a second dose given at challenge. This phenomenon was most apparent when the pre-dose-challenge dose interval was 15--60 min. Similar findings were obtained using antigen-induced histamine release in vitro from rat peritoneal cells. In these respects, ICI 74,917 was similar to disodium cromoglycate (DSCG) although DSCG appeared less effective in inducing tachyphylaxis than ICI 74,917. There was no evidence in vivo or in vitro that a high dose of either DSCG or ICI 74,917 enhanced the activity of a second low dose of either drug given at challenge.

Animals

Prophylaxis and treatment of experimental anaphylaxis in cattle by sodium meclofenamate.

Sodium meclofenamate was compared to saline for efficacy in preventing and treating experimentally induced, acute, systemic anaphylaxis in cattle. Respiratroy changes were shown to be reduced to the greatest extent. Lacrimation and collapse were not affected. The timing and routes of administration giving maximum efficacy were those which gave maximum plasma levels of the drug closest to the time of exposure of the animal to the specific antigen.

Administration, Oral